External

The leaves are slightly irritating, but it is doubtful whether any of their constituents can be absorbed by the skin.

Internal

Gastro-intestinal tract. - Digitalis is a mild gastro-intestinal irritant, and even moderate doses cause vomiting and diarrhoea in some people.

Blood. - It is not rapidly absorbed; it is not known to affect the blood.

Heart. - The first action of digitalis is to slow the beat of the heart, the diastole is prolonged, the duration of the systole is not altered, but its force is greatly increased, so much so that after large doses the heart may, in animals, be seen to become pale. because almost every drop of blood is squeezed out of it. The pulse is consequently increased in force, but retarded. If before the drug was given the heart was beating irregularly, it generally becomes regular. If the drug is taken internally, the whole of both ventricles is, in mammals, affected; but in frogs one portion of the ventricle may remain spasmodically contracted during the diastole of the rest of it. Finally the ventricles are, in frogs, arrested in systole, firmly contracted, quite pale, and unable to respond to any stimuli, but in mammals the heart finally stops in diastole. If locally applied to parts of the ventricle of the frog, only those parts to which the digitalis is applied are contracted; this is not so in mammals. The auricles are in most animals slowed by it - but the force of their beat is not much altered. In all animals large doses cause great irregularity of the auricular beat.

That these phenomena are chiefly due to the direct action of the drug on the cardiac muscle is shown by the fact that digitalis not only tonically contracts the frog's heart when applied locally, but it will even increase the force of the contraction, when applied to the isolated apex in which it is believed no nerves exist, and it acts on the embryonic heart of the chick before the nerves are developed. But the inhibitory activity of the cardiac peripheral end of the vagus is increased; for a mild stimulation of the vagi, which, before the drug was given, had no effect, will after the drug is given, stop the heart, and in warm-blooded animals digitalis does not very markedly retard the pulse, if the vagi have been cut, although it increases the force of the cardiac beat. The vagus centre in the medulla is stimulated to a less extent. Cushing has shown that the vagal action, with most of the digitalis group of drugs, begins a little before the muscular.

It has been proved that even small doses actually increase the amount of work done by the heart in a given time; thus there is a greater output at each ventricular contraction.

Vessels. - Moderate doses of digitalis produce a great rise in the blood-pressure. This is partly due to the greater cardiac force, but not entirely, for in the web of the frog's foot and the rabbit's mesentery the arterioles have been observed to contract vigorously when digitalis has been given. As this still occurrs in arterioles quite separated from the body, and through which an artificial circulation of blood containing digitalis is carried on, it is clear that the drug contracts the arterioles by direct action on their muscular coat. But as the contraction is greater in an intact animal than in one whose spinal cord is destroyed, or in whom the nerves going to the part experimented upon are divided, it is clear that digitalis also stimulates the medullary and spinal vaso-motor centres. With toxic doses the irritation of the centres and of the muscular coat of the arterioles passes on to depression, and the blood-pressure falls.

Kidney. - The effect of digitalis on the kidney is very uncertain. Most experimenters have found that in health it is diuretic, but some have not, and the same discrepancy in its action on the kidney exists in patients with heart disease, but generally in these cases it is a diuretic. The reasons for these discrepancies are that if the arterial vessels are, like the rest of the vessels in the body, tightly contracted by the drug, very little blood will come to the kidney, and very little urine will be secreted; but if the digitalis does not constrict the renal vessels markedly, the increased cardiac force and the general rise of blood-pressure will send more blood through the kidney and more urine will be excreted. Some observers have, probably incorrectly, stated that digitalin and digitoxin have a special effect in relaxing the vessels of the kidney. We have no certain knowledge of the effect of digitalis on the constitution of the urine.

Temperature. - Moderate doses have no influence on the temperature, but toxic doses cause it to fail even in health. The reason of this is unknown.

Respiration. - This is unaffected by digitalis unless poisonous doses have been given, when it begins to fail from the imperfect circulation through the respiratory mechanism.

Nervous system and Muscles. - Medicinal doses have no marked influence. Large doses will, because of the alterations in the cerebral circulation, cause headache, giddiness, and disturbances of sight and hearing. In many cases of poisoning all objects have appeared blue. In acute poisoning there is a peculiar blue color of the sclerotic

The reflex activity of the cord and motor nerves is depressed independently of the action on the circulation; sensory nerves are unaffected. Digitalis directly paralyzes muscles if given in toxic doses.

Uterus. - This organ is said to be stimulated to contract by digitalis.